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Biomedical subjects

Jeffrey T Kuvin

Publications and source records attributed to Jeffrey T Kuvin.

At least 19 recordsLinked to original sources

Extent to which accepted serum lipid goals are achieved in a contemporary general medical population with coronary heart disease risk equivalents.

This study examined lipid levels and the use of lipid-altering drugs in a contemporary general medical population without documented coronary heart disease (CHD) but with CHD risk equivalents. On the basis of present national guidelines, the following lipid values (in milligrams per deciliter) were considered optimal for this population: low-density lipoprotein cholesterol <100, high-density lipoprotein (HDL) cholesterol >or=40 in men and >or=50 in women, and non-HDL cholesterol <130 if triglycerides are >or=200. Of 44,052 active patients screened, 877 with CHD risk equivalents as defined by the Adult Treatment Panel III guidelines were identified. Most patients did not meet optimal lipid targets for low-density lipoprotein cholesterol (59%), HDL cholesterol (66%), and non-HDL cholesterol (72%). Indeed, 88% of patients did not meet >or=1 lipid goal. Statins were used in 57% of patients. In patients with low HDL cholesterol, only 4.7% were taking niacin and 4.9% fibrates. In the subgroup of patients with triglycerides >or=200 mg/dl, only 9.5% were taking fibrates and 8.2% niacin. In conclusion, the present analysis highlights the dramatic need to further improve preventive measures in a substantial proportion of high-risk patients with CHD risk equivalents.

Aged↗

Left ventricular remodelling index (LVRI) in various pathophysiological conditions: a real-time three-dimensional echocardiographic study.

BACKGROUND: Various studies have reported a close correlation between real-time three-dimensional echocardiography (RT3DE) and cine magnetic resonance imaging studies for the assessment of cardiac volumes and mass. OBJECTIVE: The aim of our study was to evaluate changes in left ventricular volumes and mass in subjects with different pathophysiological conditions. A ratio between left ventricular mass and end-diastolic volume (LVRI), detected by RT3DE, was used to describe various patterns of left ventricular remodelling. METHODS: RT3DE was performed to calculate left ventricular end-diastolic (LVEDV) and end-systolic volume (LVESV), ejection fraction (LVEF) and mass in 220 selected subjects. Of these, 152 were healthy volunteers, 19 top-level rowers, 23 patients with dilated cardiomyopathy and 26 patients with hypertrophic cardiomyopathy. Off-line analysis was performed by two independent operators by tracing manual endocardial and epicardial borders of the left ventricle through eight cutting planes. Inter- and intra-observer variability were calculated. RESULTS: Despite the increase in LV volume and mass in the rowers, LVRI remained unchanged compared with control subjects (p = 0.455), while significantly lower values were found patients with dilated cardiomyopathy (p<0.001) and significantly higher values in patients with hypertrophic cardiomyopathy (p<0.001). There was inter- and intra-observer variability. CONCLUSION: The LVRI may serve as a simple and useful indicator of left ventricular adaptation to physiological and pathological conditions.

Adult↗

Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease.

In this study, niacin was added to existing therapy for 3 months in 54 subjects with stable coronary artery disease. Average total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were similar between groups. Three months of niacin treatment increased total HDL by 7.5% and decreased triglycerides by 15% compared with baseline values (p <0.005 for each), whereas total cholesterol and LDL levels remained unchanged. Addition of niacin resulted in a 32% increase in large-particle HDL (p <0.001), an 8% decrease in small-particle HDL (p = 0.0032), an 82% increase in large-particle LDL (p = 0.09), and a 12% decrease in small-particle LDL (p = 0.008). Niacin decreased lipoprotein-associated phospholipase A2 and C-reactive protein levels (20% and 15%, respectively, p <0.05 for the 2 comparisons). No significant changes from baseline were seen in any tested parameter in subjects who received placebo. In conclusion, addition of niacin to existing medical regimens for patients with coronary artery disease and already well-controlled LDL levels favorably improves the distribution of lipoprotein particle sizes and inflammatory markers in a manner that would be expected to confer atheroprotection. The effect of altering lipoprotein particle distribution and inflammatory markers on surrogate markers of atherosclerosis and clinical cardiovascular events in this population remains unclear.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

What is the best approach for the assessment of left atrial size? Comparison of various unidimensional and two-dimensional parameters with three-dimensional echocardiographically determined left atrial volume.

BACKGROUND: Left atrial (LA) size has prognostic importance in a variety of cardiac conditions. Diameters, area, or volume derived from 2-dimensional (2D) echocardiography (2DE) are commonly used to measure LA size, but involve numerous assumptions. This study examined the accuracy of these 2DE parameters compared to 3-dimensional echocardiographic LA volume (3DV). METHODS: LA diameters, area, and volume measured from 2DE were correlated with 3DV in 118 patients with dilated cardiomyopathy, hypertrophic cardiomyopathy, or without structural heart disease. RESULTS: Diameter (anterior-posterior, superior-inferior, and medial-lateral) and 2DE area measurements had statistically significant, but modest, correlations with 3DV, and exhibited a large degree of scatter in comparison with 3DV. The 2DE-derived volume had an excellent correlation with 3DV, but consistently underestimated LA volume. CONCLUSION: The 2DE LA volume correlates better than other parameters with 3DV, but often results in underestimation. Thus, caution should be exercised when using unidimensional and 2D measurements of LA size.

Adolescent↗

Vascular endothelial dysfunction is associated with reversible myocardial perfusion defects in the absence of obstructive coronary artery disease.

BACKGROUND: The purpose of this study was to investigate whether endothelial dysfunction contributes to abnormal myocardial perfusion imaging (MPI) observed in patients without obstructive coronary artery disease (CAD). It is unclear whether reversible MPI defects detected in the absence of obstructive CAD represent underlying vascular pathology or are false-positive MPI results. Recent evidence suggests that coronary endothelial dysfunction might play a role in the pathogenesis of these defects. METHODS AND RESULTS: We prospectively recruited 36 patients with chest discomfort, reversible abnormalities on MPI, and nonobstructive or absent CAD (stenosis <50% on coronary angiography). The control group (n = 55) consisted of patients with chest discomfort and similar cardiac risk factors but with normal MPI findings. Vascular endothelial function was assessed in the brachial artery by ultrasound as the response to hyperemia and reported as percent flow-mediated dilation (FMD). Response to sublingual nitroglycerin was used as an indicator of endothelium-independent vasodilation. The patients with abnormal MPI findings and nonobstructive CAD had a significantly lower FMD (9.0% +/- 7.2%), indicating endothelial dysfunction, compared with those with similar risk factors and normal MPI findings (12% +/- 5.2%) (P = .03). Baseline brachial artery size and endothelium-independent dilation were similar between groups. On multivariate analysis, only endothelial dysfunction was predictive of reversible MPI defects. CONCLUSIONS: Patients with chest pain and reversible MPI defects but without obstructive CAD have lower FMD indicative of endothelial dysfunction, as compared with similar patients with normal MPI findings. The possibility of a causal link between reversible MPI defects and endothelial dysfunction needs further exploration.

Coronary Disease↗

High-density lipoprotein cholesterol-raising strategies.

There is a distinct inverse relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease risk. HDL-C mediates cholesterol efflux from the vasculature and promotes anti-oxidant, anti-inflammatory, and anti-thrombotic effects. There are multiple lifestyle and therapeutic interventions that raise HDL-C, and there is increasing evidence that these interventions improve cardiovascular outcomes. Recent findings regarding the role of HDL-C in cholesterol metabolism offer new strategies designed to target atherosclerosis. This review highlights the utility of existing HDL-C-raising strategies and examines new potential therapies.

Apolipoprotein A-I↗

Echocardiographic detection of intrapulmonary shunting in a patient with hepatopulmonary syndrome: case report and review of the literature.

Transthoracic echocardiography is a useful tool in the evaluation of patients with intrapulmonary and intracardiac shunts. We describe a case of a 49-year-old female with severe hypoxemia in the setting of aortic stenosis and cirrhosis of the liver. The use of agitated saline contrast during an echocardiography study helped to establish the diagnosis of intrapulmonary arteriovenous shunting consistent with the hepatopulmonary syndrome, thereby confirming the etiology of her symptoms and laboratory findings. This case report highlights the utility of echocardiography in diagnosing intrapulmonary shunts and assists in the understanding of the pathophysiology of hypoxemia in such patients.

Aortic Valve Stenosis↗

Evaluation of peripheral vascular endothelial function with a portable ultrasound device.

Endothelial function can be assessed noninvasively by imaging the brachial artery with ultrasound before and during reactive hyperemia. However, the standard ultrasound equipment typically used for this purpose is limited by size and expense of the machinery. In this study, we compared the ability of a portable ultrasound device to standard ultrasound equipment to visualize the brachial artery for purposes of assessing peripheral vascular endothelial function. The portable device provided comparable imaging of the brachial artery at rest and during hyperemia to that of standard ultrasound technology. These findings support the feasibility of noninvasive evaluation of peripheral endothelial function in the ambulatory setting.

Adult↗

Gender-based differences in brachial artery flow-mediated vasodilation as an indicator of significant coronary artery disease.

Ultrasound of the brachial artery is widely used to assess endothelial function, but whether brachial artery flow-mediated vasodilation (FMD) differs between women and men who have coronary artery disease (CAD) has not been examined. To investigate gender-based differences in brachial artery FMD as an indicator of significant CAD, FMD was measured in women and men outpatients who had CAD (coronary stenosis >50%, n = 64) and those who did not have significant CAD (n = 145). FMD in women who had CAD (n = 33, 9.1 +/- 0.8%) was higher than that in similarly aged men who had CAD (n = 31, 6.4 +/- 0.5%; p = 0.008). The FMD cutpoint that maximized sensitivity with least effect on specificity for screening CAD was 15% (91% sensitivity, 25% specificity) in women but 10% (90% sensitivity, 43% specificity) in men. If the cutpoint as defined in men were used to evaluate women, brachial artery ultrasound would fail to diagnose 42% of women who do not have significant CAD; thus, a higher FMD cutpoint is required to optimize the sensitivity of FMD for identifying women who have significant CAD compared with similarly aged men. In studies using FMD to evaluate cardiovascular risk, different standards should be applied for women and men.

Brachial Artery↗

The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis.

BACKGROUND: Statins are currently the mainstay of dyslipidemia management for the primary and secondary prevention of cardiovascular disease. Controversial concerns about the safety of the newly marketed statin rosuvastatin have been raised on the basis of premarketing studies and a few postmarketing reports. METHODS AND RESULTS: We reviewed rosuvastatin-associated adverse events reported to the US Food and Drug Administration over its first year of marketing. On the basis of prescription data obtained from IMS Health, rates of adverse event reports (AERs) per million prescriptions were calculated. Rates of rosuvastatin-associated AERs over its first year of marketing were compared with those seen with atorvastatin, simvastatin, and pravastatin over the concurrent timeframe and during their respective first years of marketing. Comparison was also made to the first year of marketing of cerivastatin. The primary analysis examined the composite end point of AERs of rhabdomyolysis, proteinuria, nephropathy, or renal failure. With either timeframe comparison, rosuvastatin was significantly more likely to be associated with the composite end point of rhabdomyolysis, proteinuria, nephropathy, or renal failure AERs. Reported cases of rhabdomyolysis, proteinuria, or renal failure tended to occur early after the initiation of therapy and at relatively modest doses of rosuvastatin. The increased rate of rosuvastatin-associated AERs relative to other widely used statins was also observed in secondary analyses when other categories of AERs were examined, including adverse events with serious outcomes, liver toxicity, and muscle toxicity without rhabdomyolysis. CONCLUSIONS: The present analysis supports concerns about the relative safety of rosuvastatin at the range of doses used in common clinical practice in the general population.

Consumer Product Safety↗

Comparison of flow-mediated dilatation of the brachial artery in coronary patients with low-density lipoprotein cholesterol levels <80 mg/dl versus patients with levels 80 to 100 mg/dl.

Testing of peripheral vascular endothelial function was performed in subjects who had coronary artery disease and a low-density lipoprotein (LDL) cholesterol level <100 mg/dl. LDL cholesterol was an independent predictor of flow-mediated dilation of the brachial artery (p = 0.010). The 63 subjects who had an LDL cholesterol level <80 mg/dl had better endothelial function (flow-mediated dilation 8.4 +/- 3.8%) than did 47 subjects whose level of LDL cholesterol was 80 to 100 mg/dl (flow-mediated dilation 6.8 +/- 4.0%, p = 0.03). The beneficial effects of LDL cholesterol levels <80 mg/dl on endothelial function were more apparent in subjects who had low levels of high-density lipoprotein cholesterol than in those who had normal levels. These data support recent reports that decreasing levels of LDL cholesterol below those currently recommended provides additional benefits and suggest that this benefit may be due in part to increased endothelial function.

Brachial Artery↗

Peripheral vascular endothelial function correlates with exercise capacity in women.

BACKGROUND: Vascular endothelial function has been observed to correlate with exercise capacity in predominantly male populations. Gender-based differences exist in the clinical course of coronary artery disease, and previous studies indicate that estrogen may influence endothelial function. These observations raise the possibility that the relationship between endothelial function and exercise capacity in women may differ from that in men. HYPOTHESIS: This study aimed to determine whether peripheral vascular endothelial function correlates with exercise capacity in women. METHODS: Women who were referred for clinically indicated exercise testing with technetium-99 myocardial perfusion imaging were consecutively recruited. To ensure a population free of exercise limitation due to ischemic heart disease, women without myocardial perfusion defects were included for analysis in this study (n = 105). Endothelial function was assessed by brachial artery ultrasound flow-mediated vasodilation (FMD). Exercise capacity was defined as the duration of exercise on a symptom-limited Bruce protocol. RESULTS: Mean FMD was 11.8 +/- 0.6%, and median FMD was 12%. Subjects with an FMD less than the median of 12% had a significantly shorter exercise time than those with FMD > or = 12% (411 +/- 17 vs. 482 +/- 24 s, p = 0.014). There was a significant correlation between FMD and exercise time (r = 0.34, p < 0.001). Age and body mass index were additional predictors of exercise time; however, the relationship between FMD and exercise time was independent of these variables. CONCLUSION: Brachial artery FMD correlates with exercise capacity in women, even in the absence of ischemic heart disease.

Adult↗

Association of estrogen receptor beta gene polymorphisms with left ventricular mass and wall thickness in women.

BACKGROUND: Left ventricular (LV) hypertrophy is a significant risk factor for cardiovascular disease. Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure. METHODS: We studied 1249 unrelated individuals, 547 men and 702 women (mean age 59 years) from the Framingham Heart Study. Eight single nucleotide polymorphisms in the genes for estrogen receptor alpha and estrogen receptor beta (ESR2) were tested for association with 5 LV measures: LV mass (LVM), LV wall thickness (LVWT), LV internal diameter at end-diastole and end-systole, and fractional shortening. Sex-specific multiple regression analyses were performed adjusting for age, weight, height, systolic and diastolic blood pressure, hypertension treatment, diabetes, and in women, menopausal status. RESULTS: In men, there was no evidence of association between the estrogen pathway polymorphisms tested and LV structure or function. In women, however, two polymorphisms, ESR2 rs1256031 and ESR2 rs1256059, in linkage disequilibrium with one another, were associated with LVM and LVWT (P = .0007 to .03); the association was most pronounced in those women with hypertension (P = .0006 to .01). The association did not appear to be explained by variation in blood pressure, plasma lipoprotein levels, or hyperglycemia. CONCLUSIONS: The ESR2 polymorphisms are associated with LV structural differences in women with hypertension in a community-based population. These data are consistent with the hypothesis that genetic factors may mediate part of the observed sex-based differences in LV structure and remodeling.

Aged↗

High-density lipoprotein cholesterol in the cardiovascular equation: does the "good" still count?

This article will discuss our current understanding of the role of HDL-C in the statin era, focusing on the question as to whether HDL-C still "counts" when determining cardiovascular risk. Epidemiologic evidence consistently demonstrates that low HDL-C is a strong and independent risk factor for CHD. The epidemiologic evidence is complimented by clinical data showing that interventions that raise HDL-C are associated with reductions in CHD risk, as well as by a growing body of experimental data demonstrating biologically plausible mechanisms that may underlie the observed clinical findings. Analyses of large statin trials also indicate that the significant and independent relationship between HDL-C and CHD risk persists despite the therapeutic effects of statins, and that HDL-C levels in statin-treated patients, both at baseline and in response to statin therapy, are relevant. Early studies on novel HDL targeting therapies are promising, but their long term safety profile and impact on clinical outcomes is yet to be determined in larger studies. Recent guidelines emphasize low HDL-C as an independent risk factor for cardiovascular disease, specifically identify HDL-C as a target for intervention, and encourage the use of HDL-C raising interventions in high-risk patients with low HDL-C levels.

Cardiovascular Diseases↗

Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia.

OBJECTIVES: We investigated the value of reactive hyperemia peripheral arterial tonometry (RH-PAT) as a noninvasive tool to identify individuals with coronary microvascular endothelial dysfunction. BACKGROUND: Coronary endothelial dysfunction, a systemic disorder, represents an early stage of atherosclerosis; RH-PAT is a technique to assess peripheral microvascular endothelial function. METHODS: Using RH-PAT, digital pulse volume changes during reactive hyperemia were assessed in 94 patients without obstructive coronary artery disease and either normal (n = 39) or abnormal (n = 55) coronary microvascular endothelial function; RH-PAT index, a measure of reactive hyperemia, was calculated as the ratio of the digital pulse volume during reactive hyperemia divided by that at baseline. RESULTS: Average RH-PAT index was lower in patients with coronary endothelial dysfunction compared with those with normal coronary endothelial function (1.27 +/- 0.05 vs. 1.78 +/- 0.08: p < 0.001). An RH-PAT index <1.35 was found to have a sensitivity of 80% and a specificity of 85% to identify patients with coronary endothelial dysfunction. CONCLUSIONS: Digital hyperemic response, as measured by RH-PAT, is attenuated in patients with coronary microvascular endothelial dysfunction, suggesting a role for RH-PAT as a noninvasive test to identify patients with this disorder.

Coronary Artery Disease↗

Risk of adverse events with fibrates.

An increased risk for adverse events was observed with gemfibrozil relative to fenofibrate, predominantly driven by an increased rate of rhabdomyolysis. This difference was especially noticeable in patients taking the combination of gemfibrozil and a statin, particularly cerivastatin.

Aged↗

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function.

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.

Age Factors↗